The focus of the candidate's research program for this Research Career Development Award proposal is the study of aging and Alzheimer's disease. The study population is 1,975 Roman Catholic sisters (nuns) who were born before 1917. Archival records will be used to reconstruct early life traits such as socioeconomic and health status of the family, cognitive ability, and attained education. About 760 of the 1,975 sisters survived to 1991 (ages 75 to 100) and will participate in annual assessments of mental and physical function. Data from the archives and annual assessments will be used to determine the relation of early life traits of life expectancy and the duration of "independent" life (able to perform self-care) and "dependent" life (unable to perform self-care). The supplemental project will examine the relation of Alzheimer's disease (AD) occurrence to both the familial and cognitive traits of early life and the pathophysiologic and cognitive characteristics of late life. These late-life characteristics include cerebrovascular atherosclerosis and its risk factors, cognitive ability, and functional brain reserve (e.g., quantity of neurons and synapses, density of senile plaques, area and location of brain infarctions, and traits of early life are associated with AD because of their relationship to functional brain reserve. We propose that diminished functional brain reserve lowers the threshold of susceptibility to AD (symptoms of Ad appear during early neuropathological stages of the diseases). Participants in this study will be from the same defined population who range from 75 year-olds who were severely demented and disabled when they died to 100 year-olds who were highly functional when they died. Each participant (and brain) has a rich source of archival data covering social, familial, cognitive, functional, and health characteristics for the entire life span. Participants are homogenous on a multitude of adult traits that usually confound non-experimental studies, such as smoking, drinking, reproductive history, and access to health care. To date, over 90 percent of sisters invited to volunteer for the study have signed consent forms (indicating a willingness to participate in all phases of the study including brain donation). Overall, this is a well defined, cooperative, and closed population in which to examine the early and late life correlates of dementia, disability, and death. Adding a biomedical supplement to the ongoing social and behavioral study is an economical method of tapping a unique resource for Alzheimer's disease research.